Bacteroides fragilis species are obligate anaerobic Gram-negative bacteria and the most common anaerobes isolated from severe human infections, such as intraabdominal sepsis and abscesses. Gorbach S L et al. (1974) in Anaerobic Microorganisms in Intraabdominal Infections (Charles C. Thomas, Springfield, Ill.), pp. 399-407; Aldridge K E (1995) Am J Surg 169:2S-7S; Polk B J et al. (1977) Ann Intern Med 86:567-71. Abscesses are a characteristic host response to infection by B. fragilis and cause considerable morbidity and mortality. Cross A S (1994) Lancet 343:248-9. Previous investigations in animal models have demonstrated that capsular polysaccharides (CPs) isolated from B. fragilis are capable of modulating the course of abscess formation via a T-cell-dependent mechanism. U.S. Pat. No. 5,679,654; U.S. Pat. No. 5,700,787; Brubaker J O et al. (1999) J Immunol 162:2235-42; Tzianabos A O et al. (1995) Infect Immun 62:4881-6; Tzianabos A O et al. (1995) J Clin Invest 96:2727-31; Kalka-Moll W M et al. (2000) J Immunol 164, 719-24; Tzianabos A O et al. (2000) J Biol Chem 275, 6733-40. More important, B. fragilis CPs can confer protection against a wide variety of abscess-inducing microorganisms, including B. fragilis itself, Staphylococcus aureus, Streptococcus pneumoniae, and other synergistic microbes. Brubaker J O et al. (1999) J Immunol 162:2235-42; Tzianabos A O et al. (1995) Infect Immun 62:4881-6; Tzianabos A O et al. (1995) J Clin Invest 96:2727-31; Kalka-Moll W M et al. (2000) J Immunol 164, 719-24; Tzianabos A O et al. (2000) J Biol Chem 275, 6733-40. It is interesting to note that, in contrast to the paradigm that carbohydrate antigens are T-cell independent, B. fragilis CPs activate T cells to proliferate and elicit cytokine responses. Tzianabos A O et al. (2000) J Biol Chem 275, 6733-40; Stein K E (1992) J Infect Dis 165:S49.
Immunomodulating CPs from B. fragilis are structurally distinctive in that they are zwitterionic polysaccharides (ZPSs), carrying a high density of both positive and negative charges. Previous studies have identified two ZPSs, PS A (hereinafter PS A1) and PS B, from the capsule of B. fragilis 9343 (Pantosti A et al. (1991) Infect Immun 59:2075-82; Baumann H et al. (1992) Biochemistry 31:4081-9; Tzianabos A O et al. (1993) Science 262:416-9), both of which are potent activators of T cells in vitro and protect animals against abscess formation in vivo. Brubaker J O et al. (1999) J Immunol 162:2235-42; Tzianabos A O et al. (1995) Infect Immun 62:4881-6; Tzianabos A O et al. (1995) J Clin Invest 96:2727-31; Kalka-Moll W M et al. (2000) J Immunol 164, 719-24. The charges are critical determinants of immunologic activity, as chemical neutralization of these groups abolishes T-cell stimulation. Brubaker J O et al. (1999) J Immunol 162:2235-42; Tzianabos A O et al. (1995) Infect Immun 62:4881-6; Tzianabos A O et al. (1995) J Clin Invest 96:2727-31; Kalka-Moll W M et al. (2000) J Immunol 164, 719-24. More recent studies suggest that T-cell-mediated abscess modulation is a common property of ZPSs. Tzianabos A O et al. (2000) J Biol Chem 275, 6733-40.
Realizing that molecular charges of ZPSs are critical determinants of their immunological effects, while the primary structures of these compounds differ significantly, a need remains for understanding details of the structures of different ZPSs from various strains of B. fragilis, particularly as they may relate to the unique immunological properties of these polysaccharides.